Section of Physiology and Genetics, Department of Biology, University of Turku, 20500 Turku, Finland.
Research Programs Unit, Translational Cancer Biology Program, University of Helsinki, 00290 Helsinki, Finland.
eNeuro. 2019 Aug 22;6(4). doi: 10.1523/ENEURO.0003-19.2019. Print 2019 Jul/Aug.
The mammalian PIM family of serine/threonine kinases regulate several cellular functions, such as cell survival and motility. Because PIM expression is observed in sensory organs, such as olfactory epithelium, we now wanted to explore the physiological roles of PIM kinases there. As our model organism, we used the nematodes, which express two PIM-related kinases, PRK-1 and PRK-2. We demonstrated PRKs to be true PIM orthologs with similar substrate specificity as well as sensitivity to PIM-inhibitory compounds. When we analyzed the effects of pan-PIM inhibitors on sensory functions, we observed that PRK activity is selectively required to support olfactory sensations to volatile repellents and attractants sensed by AWB and AWC neurons, respectively, but is dispensable for gustatory sensations. Analyses of -deficient mutant strains confirmed these findings and suggested that PRK-1, but not PRK-2 is responsible for the observed effects on olfaction. This regulatory role of PRK-1 is further supported by its observed expression in the head and tail neurons, including AWB and AWC neurons. Based on the evolutionary conservation of PIM-related kinases, our data may have implications in regulation of also mammalian olfaction.
哺乳动物的 PIM 丝氨酸/苏氨酸激酶家族调节多种细胞功能，如细胞存活和运动。由于 PIM 的表达存在于感觉器官中，如嗅上皮，我们现在想探索 PIM 激酶在那里的生理作用。作为我们的模式生物，我们使用了线虫，它表达两种与 PIM 相关的激酶，PRK-1 和 PRK-2。我们证明 PRK 是真正的 PIM 同源物，具有相似的底物特异性和对 PIM 抑制化合物的敏感性。当我们分析泛 PIM 抑制剂对感觉功能的影响时，我们观察到 PRK 活性选择性地需要支持 AWB 和 AWC 神经元分别感知挥发性驱避剂和引诱剂的嗅觉感觉，但对味觉感觉是可有可无的。- 缺陷突变体菌株的分析证实了这些发现，并表明 PRK-1 而不是 PRK-2 负责观察到的嗅觉效应。PRK-1 的这种调节作用进一步得到了其在头部和尾部神经元（包括 AWB 和 AWC 神经元）中的表达的支持。基于 PIM 相关激酶的进化保守性，我们的数据可能对哺乳动物嗅觉的调节具有重要意义。
